Ammonia → HCID 18975712, compound

HRID 2393461Notes

Reaction equation

HRID 2393461 reaction equation
[CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([CH2:7][CH2:8][N:9]=[C:10]2[C:13]2([C:16]3[CH:20]=[CH:19][S:18][CH:17]=3)[CH2:15][CH2:14]2)=[CH:5][C:4]=1[CH3:21].C(OC(N1CCC[C@H]1C(O[BH-](OC(=O)[C@@H]1CCCN1C(OC(C)(C)C)=O)OC(=O)[C@@H]1CCCN1C(OC(C)(C)C)=O)=O)=O)(C)(C)C.[Na+].[C:69]([OH:74])(=[O:73])[C:70]([OH:72])=[O:71].N>ClCCl.CCOCC>[C:69]([OH:74])(=[O:73])[C:70]([OH:72])=[O:71].[CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([CH2:7][CH2:8][NH:9][CH:10]2[C:13]2([C:16]3[CH:20]=[CH:19][S:18][CH:17]=3)[CH2:15][CH2:14]2)=[CH:5][C:4]=1[CH3:21]

Participants

7

Reactant 4

HCID 222AmmoniaHCID 971Oxalic Acid2×HCID 18975665HCID 18975665, compoundHCID 23679383HCID 23679383, compound

Product 1

HCID 18975712HCID 18975712, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 7-methoxy-6-methyl-1-[1-(3-thienyl)cyclopropyl]-3,4-dihydroisoquinoline (2.0 g, prepared in a similar manner to that described in Example 6) in dichloromethane (87 ml) was added slowly to an ice-cooled stirred mixture of sodium tris[(S)-N-(tert-butoxycarbonyl)prolyloxy]borohydride (11.4 g) in dichloromethane (70 ml). After standing at about 4° C. for 2 days a further portion of the reducing agent (2.0 g) was added and the mixture stirred at ambient temperature for 3 hours, then saturated aqueous oxalic acid solution (150 ml) was added. This mixture was stirred for 1 hour then basified with concentrated aqueous ammonia solution and extracted with dichloromethane (4×100 ml). The combined extracts were washed with water (100 ml) then brine (100 ml) then dried over magnesium sulphate and the solvent removed in vacuo to give a pale orange gum. The gum was dissolved in ether (150 ml) and treated with a solution of oxalic acid in ether (0.43M; 20 ml) and the resulting precipitate filtered then recrystallised from ethanol to give a single enantiomer of 7-methoxy-6-methyl-1-[1-(3-thienyl)cyclopropyl]-1,2,3,4-tetrahydroisoquinoline oxalate (1.2 g) which was used without further characterisation.

Workup

  1. temperaturecooled
  2. additiona further portion of the reducing agent (2.0 g) was added
  3. stirringthe mixture stirred at ambient temperature for 3 hours
  4. stirringThis mixture was stirred for 1 hour
  5. extractionextracted with dichloromethane (4×100 ml)
  6. washThe combined extracts were washed with water (100 ml)
  7. dry with materialbrine (100 ml) then dried over magnesium sulphate
  8. customthe solvent removed in vacuo
  9. customto give a pale orange gum
  10. filtrationthe resulting precipitate filtered
  11. customthen recrystallised from ethanol

Sources & evidence

ORD record
ord-a0504dca38ba4b9f8a81b92b13eda95f
Source dataset
uspto-grants-1998_09
Patent number
US05807868

Reaction notes

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